Portal hypertension

Current Status

Abraham Shaked MD PhD

Portal Hypertension

• Defined as an increase in portal vein pressure

to exceed 6 mmHg

• It is the underlying process responsible for the

most common complications of cirrhosis:

– Ascites

– Variceal bleeding

– Hepatic encephalopathy

Portal circulation

Classification of portal hypertension

(PHTN)

Pre-hepatic

PHTN

Portal v thrombosis

Intrahepatic

PHTN

Presinusoidal

Sarcoidosis

PBC

Schistosomiasis

Sinusoidal

Cirrhosis

Alcoholic Hepatitis

Postsinusoidal

Sinusoid obstruction

syndrome (VOD)

Post-hepatic

PHTN

Budd-Chiari Syndrome

Rt heart failure

Constrictive pericarditis

IVC web

- Fibrosis in the space of Disse

- Compression by regenerative nodules

and fibrous bands

- Swelling of hepatocytes

Histological

Clinical Non-cirrhotic Compensated Compensated Decompensated

Symptoms None None (no varices) None (varices present)Ascites, VH,

encephalopathy

Sub-stage - Stage 1 Stage 2 Stages 3 and 4

Hemodynamic (HVPG,

mmHg)

BiologicalFibrogenesis and

AngiogenesisScar and X-linking

Thick (acellular) scar

and nodulesInsoluble scar

Classification of Chronic Liver Disease

>6 >10 >12

F1-F3 F4 (Cirrhosis)

Garcia Tsao G et al Hepatology 51:145-9;2010

Cumulative Proportion of Patients Transitioning from Compensated to Decompensated Stage Over Time

Pro

po

rtio

n o

f P

atie

nts

1.00

0.75

0.50

0.25

0.00

Pts at risk 806 513 402 302 243 217

months0 24 48 72 96 120

D’Amico G et al. J Hepatol. 2006;44:217-231.

Consequences of PHTN: Ascites

and Hepatorenal SyndromeCirrhosis

Portal HTN

Splanchnic vasodilation

Incr Spl capillary pressure Arterial Underfilling

Na & Water Retention

Impaired free water excretion

Renal vasoconstrictionIncr lymph production

NO

ADH

Angiotensin II

Aldosterone

Norepinephrine

Ascites Hyponatremia Hepatorenal

syndrome

Hypotension

Consequences of PHTN: Varices

and Hepatic Encephalopathy

• Most common sites portosystemic collaterals

- GE junction and proximal stomach:

Gatroesophageal varices

- Umbilical vein: Caput medusae

- Rectum: Rectal varices

• Consequences:

- Increased pressure in collaterals resulting in

rupture: variceal bleeding

- Shunting of gut derived toxins (ammonia)

away from the liver: hepatic encephalopathy

Gastroesophageal varices

Small varices

< 5 mm

Large varices

> 5 mmNo varices

7-8%/year 7-8%/year

Natural history of varices in cirrhosis

Merli et al. J Hepatol 2003;38:266

VARICES INCREASE IN DIAMETER PROGRESSIVELY

• Usually develop as HVPG exceeds 10-12 mmHg

• Tend to grow with time

Cirrhosis35-80 %

Risk of Esophageal Varices

25-40 %

Die

15-20 %80-85 %

Survive

Rebleed

70 %

Bleed

Predictors of variceal bleeding

• Esophageal varices do not usually bleed

until HVPG > 12mmHg

• Bleeding rate: 5-15% / yr

• Risk of bleeding increases:

- Large Varices

- Red marks

- Child B/C

• Mortality of 20 %

• HVPG > 20 mmHg predicts a higher

mortality from variceal bleed (64% at 1 yr)

Baveno IV International Consensus Workshop Staging System for Cirrhosis:

1-Year Outcome Probabilities

NO VARICES

NO ASCITES

VARICES

NO ASCITES

ASCITES

VARICES

BLEEDING

ASCITES

DEATH

Stage 1

Stage 2

Stage 3

Stage 4

Co

mp

en

sa

ted

De

co

mp

en

sate

d

1%

3.4%

20%

57%

4.4%7%

6.6% 4%

7.6%

D’Amico G et al. J Hepatol. 2006;44:217-231.

Non-Selective Beta-Blockers in primary prophylaxis

Bleeding rate Control Beta-blocker Absolute rate(~2 year) difference

All varices 25% 15% -10%

(11 trials) (n=600) (n=590) (-16 to -5)

Large varices 30% 14% -16%(8 trials) (n=411) (n=400) (-24 to -8)

Small varices 7% 2% -5%(3 trials) (n=100) (n=91) (-11 to 2)

D’Amico et al., Sem Liv Dis 1999; 19:475

NON-SELECTIVE BETA-BLOCKERS PREVENT FIRST VARICEAL HEMORRHAGE

• If there are large varices on EGD

- β blockers or EVL

EVL: Q1-2 wks until obliteration, repeat at

1-3 months, then Q 6-12 months

• Once on β blocker for primary prophylaxis,

endoscopy not needed unless there is

need to stop βblocker or GI bleed

Primary prophylaxis for

variceal bleeding

Management of acute

variceal bleeding• Resuscitate:

- IV access, fluids, blood products

- Do not overtransfuse! Target Hb 8 g/dL

• Prophylactic antibiotics x 7 days

• IV Octreotide for 3 - 5 days

Endoscopy / EVL as soon as stabilized

• 10-20% of variceal bleeds are uncontrolled

with the above measures: TIPS

Survival, According to Transfusion Strategy

Villanueva C, et al. N Engl J Med 2013;368:11-21

5

12 11

24

9

22 22

811

0

5

10

15

20

25

Death from anycause within 45

days

Patients withcirrhosis

Bleeding fromesophageal varices

Balloon therapies TIPS

%

Restrictive Strategy

Liberal Strategy

Hemoglobin threshold for transfusion: Randomized trial of restrictive versus liberal transfusion strategies

for acute upper gastrointestinal bleeding Study Outcomes

Villanueva C, et al. N Engl J Med 2013;368:11-21

Restrictive strategy: Transfuse when Hg below 7g/dLLiberal strategy: Transfuse when Hg below 9g/dL

p=0.02p=0.04

p=0.03

p=0.05p=0.02

Blood Transfusion Requirement 15 % Vs.51%

P <0.001

Probability of Remaining Free of Recurrent Variceal Hemorrhage

Hou M-C et al., Hepatology 2004; 39:746

Prophylactic antibiotics (n=59)

%free of

variceal

bleed

1.0

0.6

0.2

0.8

10

No antibiotics (n=61)

02 3 12 30

Follow-up (months)

18 24

0.4

PROPHYLACTIC ANTIBIOTICS PREVENT EARLY VARICEAL REBLEEDING

Gastric Varices

Rx same

as EV

Can be

seen in

Spl. v.

thrombosis

Bleeding gastric fundus

varices

• Tend to be larger, more tortuous, deeper

vessels than EV: present a challenge for

endoscopic therapy

• Can bleed at lower HVPG

• Best endoscopic therapy: cyanoacrylate

injection, but not widely available and

cumbersome

• Low threshold for TIPS in bleeding GV in

the fundus

Transjugular Intrahepatic Portosystemic Shunt

(TIPS)

in the Setting of Intrahepatic and Post-hepatic

Portal Hypertension

PresinusoidalPBC

Sinusoidal

HCV, ETOH

Post-sinusoidal/Post-hepatic

BCS

Outcomes after early TIPS

• dose of propranolol

• use of nitrates

• use of uncovered stents

• exclusion of those with advanced liver disease

García-Pagán JC et al. N Engl J Med 2010;362:2370-2379.

The Blakemore Tube

Portal Vein Thrombosis• Portal vein thrombosis:

• Incidence in compensated disease: 0.6% to 5%

• Incidence in advanced disease: up to 40%

•Risk factors for PVT:• Recurrent liver decompensation

• History of infection, bleeding, endoscopic treatment

• Abdominal surgery (eg. splenectomy)

Ascites

Fatigue

Poor quality of life

Muscle wasting

Umbilical hernia rupture

Hydrothorax

SBP

Hepatorenal Syndrome

Cirrhotic Ascites – Survival

20

40

60

80

100

1 2 3 4 5 6

YearsOnset

Survival

(%)

Management of Ascites

First Line Therapy Second Line Therapy

Tense ascites

Paracentesis

Sodim restriction ( 2 Gm/24 Hrs) and diuretics

Non-tense ascites

• Repeated Large volume

paracentesis (LVP)

•TIPS ? Early

• Liver Transplantation

Refractory Ascites 10 %

•Diuretics: Spironolactone 100 mg/day, furosemide 40 mg/day or

bumetanide 1 mg a day.

•Uptitrate stepwise to spironolactone 400 mg/day, furosemide 160

mg/day or bumetanide 4 mg/day as long as it is tolerated

•Post paracentesis albumin infusion

may not be necessary for < 5 liters removed

• Albumin infusion of 6-8 gm/liter of fluid

removed is a consideration for repeated LVP

20

40

60

80

100

1 2 3 4 5 6

YearsOnset

Survival

(%)

Ascites Survival: Only improved by liver transplant

After Liver Transplant

Surgical Resection of HCC in Cirrhosis

(not to be done by the general surgeon)

0

1020

30

4050

60

70

8090

100

0 20 40 60 80

Months

Pro

ba

bilit

y (

%)

No Portal pressure, Bili <1

Portal pressure, Bili <1

Portal pressure, Bili 1

Llovet JM, et al. Hepatology 1999;30:1434–1440.

Patients selected by Mazzafero

Criteria and Child’s A cirrhosis

Life with Minimal Residual Liver

Reserve

• Stable 49 yrs with PBC who is on the transplant list with MELD of 14

• Underwent emergency repair of incarcerated umbilical hernia (no need for bowel resection)

• 1 week post-op

– Severe ascites

– HRS

– MELD 29

• 2 weeks post-op undergoes successful OLT